Impel NeuroPharma is developing a nose-to-brain drug delivery device to enable drugs to bypass the blood brain barrier (BBB) in humans. This Phase II SBIR aims to develop robust, non-custom, and affordable devices for use in preclinical studies that makes the technology more accessible to researchers everywhere. During this project, Impel will be assisted by Drs. William Frey and Leah Hanson at HealthPartners Neuroscience Research, who are experts in nose-to-brain drug delivery. Development of neurological and mental health drugs often requires preclinical testing in multiple animal models to demonstrate efficacy and safety and to elucidate mechanisms. Drug delivery to the central nervous system (CNS) to target neurological diseases is particularly problematic because the blood-brain barrier (BBB) prevents most compounds from reaching the brain from blood. While other methods of animal CNS delivery exist, these methods are invasive, not precise, or are not easily translated to clinical use. Overall, the difficulty of distributing drugs to the CNS severel limits drug development efforts. Impel's novel Precision Olfactory Delivery (POD) device allows non-invasive, targeted delivery of drugs and biologics to the CNS using the nose-to-brain route of the olfactory region to bypass the BBB. The POD device is ideal for preclinical animal studies because it precisely targets the CNS without disrupting the BBB and is scalable across a spectrum of animal models. Impel has promising POD device data in multiple preclinical models and in humans. Commercial interest in this product has been confirmed by large pharmaceutical companies and academic laboratories who have already set up agreements to use the POD device. This Phase II project will greatly decrease POD device prices, make them more accessible, and increase the number of CNS therapeutics investigated via the nascent and promising nose-to-brain pathway. As more therapeutics are investigated, more CNS disease treatments should become available to the public. In Phase I, feasibility was demonstrated and the primary milestone was achieved, as Impel developed primarily molded versions of POD devices that are not significantly different from hand-made prototypes (e.g., olfactory region dose deposition was less than 10% different than bench-use POD devices). Additionally, testing tools were created for continued development, including preclinical nasal models, a deposition testing stage, and an impact force testing apparatus. Impel has confirmed commercial interest in the proposed Phase II project from academics and industry, including multiple research labs and a large pharmaceutical company. In this Phase II project, mouse, rat, and primate POD devices will be refined. Impel will develop high- volume molds and a semi-automated assembly process (Aim 1), perform in vitro validation (Aim 1), perform in vivo validation (Aim 2), develop professional training materials (Aim 3), and optimize training materials so target end-users can successfully deposit drugs in vivo (Aim 3). This project will take two years to complete.